Liquid Fraction Collector for Liquid Chromatography System

ABSTRACT

Disclosed is a fraction collector for dispensing liquids into plural receptacles (P 1 ,P 2 ) arranged in a two dimensional array. The fraction collector comprises a table ( 22 ) for supporting said receptacles, and an arm supported above the table, in tum supporting a liquid dispenser ( 35 ), the fraction collector arm is rotatable about an arm axis (C) and the liquid dispenser is movable along the arm on a carriage  34  ( FIG. 2 ). Thereby, the dispenser is low cost and is repositionable simply above the receptacles as a result of said rotation and as a result of said movement along the arm, without occupying too much laboratory bench space.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation of and claims the priority benefit ofPCT/EP2017/051867 filed on Jan. 27, 2017, which claims priority benefitof Great Britain Application No. 1601667.7 filed Jan. 29, 2016. Theentire contents of which are hereby incorporated by reference herein.

FIELD OF THE INVENTION

The present invention relates to fraction collectors, for examplefraction collectors used in the field of liquid chromatography forsequential dispensing of liquids from a source, typically collectedfraction by fraction in a plurality of adjacent receptacles in acassette or cassettes over a time period as the chromatography processprogresses.

DESCRIPTION OF RELATED ART

A fraction collector is a device used for dispensing a liquid into anumber of receptacles. Traditionally receptacles such as test tubes arefed towards a dispensing means one by one, for example on a conveyor ortrack.

More versatile fraction collectors have been disclosed. For example U.S.Pat. Nos. 8,858,899 and 4,422,151 show an X-Y table mechanism is used tosupply multiple receptacles, wherein, collecting tubes are arranged in arectangular grid pattern and an outlet conduit is positioned over eachcollecting tube by a rectilinear positioning movement. In such fractioncollectors, herein referred to as “X-Y-collectors”, it is usually theoutlet conduit that is moved with respect to the collecting tubes.Another mechanism is described in U.S. Pat. No. 4,077,444 which shows anX-Y-collector wherein both a receptacle supporting table and a deliveryhead are moved linearly, in transverse directions with respect to eachother.

Numerous other fraction collectors are known, including a rotatablymounted turntable for supporting a plurality of collection tubes, forexample U.S. Pat. Nos. 4,862,932 and 6,450,218. In fraction collectorsof the turntable type, a liquid is sequentially discharged into thecollection tubes through an outlet conduit, such as a hollow needle. Theoutlet conduit is mounted on an arm reaching over the turntable.Typically, the arm can swing around a vertical post to be positionedover different radial rows of collecting tubes. These fractioncollectors are described herein as turntable fraction collectors.

There is a general need to provide a fraction collector which is ruggedand reliable for use in experimental chromatography, where multipleexperiments take place usually on a laboratory bench and where space isoften limited. So the space occupied by the collector is important.

There is also a drive to standardise laboratory receptacles and sostandardised microplates, such as those sold under the trade name‘Microtiter’ are popular for holding liquids. The inventors haverecognised that dispensing fractions into such standardised microplatesallows more convenient subsequent processing. One popular microplate has96 receptacles known as wells in an eight by twelve, two dimensionalorthogonal an-ay. Such plates typically have dimensions of about 85 mmby 128 mm, thus, taking into account the thickness of the plasticsmoulded well walls, each well has an opening of about 8 mm across. Theheight of the wells can be about 45 mm. If the wells are deep enough, amillilitre or so (1 ml-1.5 ml), of fluid can be collected in each well.

A conventional X-Y-collector has a table for holding the receptacles,and is further equipped with means for moving a dispensing tube over andbetween the receptacles. Typically, the moving of the dispensing tube isachieved by the use of a set of stepping motors. However, these X-Ymachines take up a relatively large area on the bench because, thelinear drives needed for an X-Y collector occupy more volume than arotary drive so tend to take up more space on the laboratory bench. Evenwhen the receptacle table is moved in the X and Y directions, and thedispensing head is kept stationary, further valuable bench-space islost.

The turntable fraction collector is useful in many applications and isgenerally more space efficient because the rotational drives take upless space than linear drives needed for X-Y collectors. However,X-Y-collectors are more suitable when handling a large number ofreceptacles formed in microplates, because they can operate in the samelinear directions as the microplate an-ay. Conventional turntablefraction collectors cannot handle such microplates.

Compared to the turntable collector, a X-Y-collector requires a longerattachment tubing, since the equipment providing the liquid isstationary with respect to the receptacles, and the tubing therefore hasto follow the dispensing tube to any receptacle. Especially inhigh-resolution liquid chromatography, this long tubing is adisadvantage because the long travelling distance of the liquids in thetube gives the initially separated components in the liquid a longertime period to diffuse within the liquid flow, and consequently theprecision of the separation is negatively affected.

SUMMARY OF THE INVENTION

Embodiments of the invention described herein address the need for aspace saving fraction collector with the ability to dispense into amicroplate formed as a two dimensional array of closely spaced wells.

Embodiments of the invention described herein address the need for areliable and rugged, yet small fraction collector.

Embodiments of the invention described herein address the need for a lowcost fraction collector.

The invention provides a fraction collector according to claims 1 and 10having preferred features defined by claims dependent on claims 1 and 10respectively.

An embodiment of the fraction collector according to the inventionincludes a table for supporting a liquid receiving plate including a twodimensional array of liquid receptacles, an arm rotatably mounted formovement above the table and a carriage supported on the arm for linearmovement relative to the arm, said carriage supporting a liquiddispenser adapted for dispensing liquids movable in a two dimensionalplane above the table for dispensing liquids into said receptacles.

The embodiment of the traction collector mentioned immediately aboveincludes a first drive motor operative to rotate the arm , and a seconddrive motor operative to move the carriage, each drive motor beinglocated under the table.

The invention extends to any combination of features disclosed herein,whether or not such a combination is mentioned explicitly herein.Further, where two or more features are mentioned in combination, it isintended that such features may be claimed separately without extendingthe scope of the invention.

Further scope and applicability of the present invention will becomeapparent from the detailed description. However, it should be understoodthat a detailed description and specific examples while indicatingpreferred embodiments of the invention are given by illustrations only.The invention, together with its objects and the advantages thereof, maybe understood better by reference to the following description taken inconjunction with the accompanying drawings, in which like referencenumerals identify like elements in the Figures.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention can be put into effect in numerous ways, illustrativeembodiments of which are described below with reference to the drawings,wherein:

FIG. 1 shows a perspective view of an embodiment of a fraction collectoraccording to the present invention;

FIG. 2 shows a further perspective view of the fraction collector shownin FIG. 1;

FIGS. 3, 4 & 5 each show a plan view of the collector shown in FIG. 1,with the motions of the parts superimposed.

FIG. 6 shows a perspective sectional view of the fraction collectorshown in FIG. 1;

FIG. 7 shows details of an arm component of the fraction collector shownin FIG. 1;

FIG. 8 shows a schematic representation of the sectional view shown inFIG. 6;

FIG. 9 shows a perspective view of another embodiment of the invention;and

FIG. 10 shows a sectional view through the middle of the embodimentshown in FIG. 9.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

An embodiment of a fraction collector 10 is shown in the figures.Referring to FIG. 1, the fraction collector 10 includes a hollow base 20having a table top 22 for receiving two microplates P1 and P2 and astatic pedestal 40 extending upwardly from the table so as to be betweenthe two plates, which in tum supports an arm 30, rotatable on thepedestal 40 and above the microplates P1 and P2. The pedestal 40 thussits mid-way along the width of the table and to one side of the table,allowing two microplates to sit on the table, one on each opposing sideof the table/pedestal. The arm 30 supports a repositionable carriage 34which in turn supports a liquid dispenser 35 above the microplates. Thedispenser 35 is positionable above any one of a plurality of liquidreceptacles, herein called wells, W1 and W2 of the microplates P1 and P2for dispensing liquids into those wells. The dispenser 35 is fed by aflexible tube 36 shown only partially, supplied, in this embodiment, bychromatographic equipment 100.

FIG. 2 shows the same collector 10, and also shows a bottom plate 24which, together with the unitarily moulded housing 20 and pedestal 40,provides protection against liquid ingress into the housing,particularly if liquid is spilled onto the table 22.

FIG. 3 shows the swinging motion attainable by the rotation of the arm30. Arrow R represents the arcuate movement of the arm 30 about centreof rotation defined by axis C which is perpendicular to the table 22.Thus the dispenser 35 can be positioned in any position in the arc.

FIG. 4 shows the further generally linear motion attainable by movementof the dispenser along the arm 30 in the direction of arrow L. Thelinear movement in the direction of arrow L occurs in use preferablyconcurrently with the arcuate moment described above, but sequentialmovement is possible also. Thereby, as a result of movements in thedirection of arrow R and arrow L, the dispenser 35 is positionable andrepositionable over any one of the wells W1 or W2, for dispensing liquidinto those wells.

Taken further, it will be appreciated that the arm may swing through 360degrees as shown in FIG. 5. This means that, if the table 22 isextended, using an extension 22′, a further microplate P3 can be mountedto the extension 22′ and can be used to collect further fractions ofliquid if needed. The slight disadvantage of this embodiment is thatfurther bench space would be needed.

FIGS. 6, 7 and 8 illustrate the mechanisms used to obtain he desireddispenser movements. FIG. 6 is a section of the collector housing 20taken along the plane IV-IV in FIG. 4, but with the arm 30 positionedover the sectional plane IV-IV so that its internal features can bebetter viewed in FIG. 6. The arm 30 includes a rigid arm member 31supporting the carriage 34 which holds the dispenser 35 (FIG. 1). Thecarriage 34 extends into a slot 31 a in the arm member 31, and thedispenser 35 will be attached to the lower end of the carriageprotruding from the slot 31 a. The arm member 31 is mounted on a supportcylinder 42 which is driven to rotate by a predetermined angle aboutcentre line C as described more fully below to cause arcuate movement ofthe arm 30 at least about arc R (FIG. 3). The cylinder 42 is supportedon a pair of spaced bearings 41, which are in turn supported on thepedestal 40. Inside the cylinder 42 is a drive shaft 38 which is drivento rotate about centre line C coaxially with the cylinder 42. Thismotion moves the carriage 34 and dispenser 35 in a linear manner asdescribed in more detail below.

More details of the mechanisms are shown in FIGS. 7 and 8. FIG. 7 showsthe arm 30 with the cover 32 removed, revealing the arm member 31mounted to the cylinder 42 for rotational movement about axis C. Fixedto the top of the drive shaft 38 is a toothed upper carriage drivepulley 33, which can rotate independently of the arm member 31. Thecarriage drive pulley 33 in use translates a toothed carriage drive belt38 a. The carriage belt 38 a is held taught by an additional arm pulley37 at the distal end of the arm member 31 and by a tensioner pulley 33 aacting on the outside face of the belt 38 b between the two pulleys 33and 37. The carriage 34 is mounted on a linear bearing 39 mounted to thearm member 31, and is attached to the carriage belt 38 a, such thatmovement of the carriage belt 38 a via a drive pulley 33 and a driveshaft 38 causes linear movement of the carriage 34 along the bearing 39in the direction of arrow L (FIG. 4), and so the position of thecarriage 34 and the dispenser 35 can be changed.

FIG. 8 shows more details of the mechanisms, in schematic form. Driveshaft 38 can be rotated by means of a toothed lower carriage drivepulley 52 connected to a stepper motor 53 via a further carriage drivebelt 54. The stepper motor 53 has an output pulley 53 a which can besmaller than the drive pullet 52 to provide slower but more accuratecarriage movements if needed, although other ratios, for example a 1:1ratio as shown in FIG. 6, could be employed. Likewise the rotation ofthe whole arm 30 is brought about by rotation of an arm pulley 55,driven by a toothed belt 57 in turn driven by the output pulley 56 a ofan arm driving stepper motor 56. Again the output pulley 56 a is smallerthan the driven pulley 55 to reduce speed and increase accuracy, butother ratios could be used, for example a 1:1 ratio as shown in FIG. 6.Electrical parts including the drive stepper motors 53 and 54 togetherwith known stepper motor control electronics 27, are enclosed within thehousing 20 in the space 26 under the table 22, closed by the base plate24. This not only provides a compact arrangement, but also inhibitsliquid ingress into the electrical parts.

In operation microplates P1 and P2, for example, are mounted to thetable 22 in complementary register slots, or channels 60 which match thefeatures on the underside of the microplates P1 and P2. The controlelectronics is used to control the stepper motors such that thedispenser, translates signals supplied by the chromatographic equipmentinto the stepper motor signals needed to position the dispenser 35sequentially above the known positions of the wells of a respectivemicroplate by movement of the dispenser 35 in a two dimensional planeover the wells, the swept area of which is shown in FIG. 5. Although itis not essential, the control electronics 27 can include amicrocontroller to compute simple stop-go type operational signals fromthe chromatographic equipment 100 into the instructions necessary forstepper motor movements to provide correct dispenser positioning, andcan provide feedback of the resting position of the dispenser and or aconfirmation signal to a pump or valve of the equipment 100, to allowfilling of the well when the dispenser is correctly positioned.

Although the illustrated orthogonal two dimensional array of wells ispreferred, it is possible that other well patterns could be employed,with suitable alterations to the running of the electronics 27. Forexample the wells could be arranged in staggered rows such that roundedwells can be closer together.

It should be noted that the illustration of FIG. 8, is schematic, inthat no details of any connecting or attaching means are shown. It is ofcourse obvious for anyone skilled in the art that the components showncould be formed and assembled in numerous ways, each one selected tosuit the application at hand, a more detailed example of that assemblybeing shown in FIG. 6. Of course, the rotating movements shown could betransferred by any suitable means other than a belt transmission, suchas a chain transmission, a gear transmission, a flexible drive shaft, orsuitable four-bar linkages.

One variant 10′ of the fraction collector 10 is shown in FIGS. 9 and 10where components having a function which is the same or similar to thatof the fraction collector 10 described above have like referencenumerals. FIG. 9 shows a base 20 having a central pedestal 40,privotably supporting an arm 30′, along which can slide a liquiddispenser 35, fed by a capillary tube 36 for dispensing into collectionmicroplates P1 and P2, all as described above with reference to FIGS. 1to 8. However, this embodiment has a modified arm 30′, including acentral slot 70 in which the dispenser 35 travels in a driven linearmanner in use.

FIG. 10 shows the slot 70 in more detail. The mechanism for moving thedispenser 35 along the arm 30 is similar to that described above, i.e. atoothed belt 33 held taut between two pulleys 33 and 37, one of which(33 in this case) is driven, except that the carriage 34′ which isattached to the belt is made much smaller and so is less bulky than thecarriage 34. In this variant the travel of the dispenser 35 can beincreased if needed because the carriage is now smaller. In addition,the dispenser is less likely to be knocked or damaged because it isprotected in part inside the arm 30′. In this variant, a linear bearingis used to keep the dispenser in the correct position as describedabove, although in a lower cost version (not shown) it is possible thatthe slot 70 supports the dispenser 35 and carriage 34′ without such abearing.

It is obvious for anyone skilled in the art that many variations of theinvention are possible within the scope of the invention. Suchvariations include, but are not limited to, the type of driving meansfor the arm 30 and carriage 34, such as DC motors with gear boxes, leverarms driven by linear movements from, for example a hydraulic orpneumatic cylinder or linear drives.

Other omissions, additions or modifications are possible to theembodiments described without departing from the scope of the inventionclaimed.

1. A fraction collector for dispensing liquids into plural receptaclesarranged in a two dimensional array, the fraction collector comprising atable for supporting said receptacles, and an arm supported above thetable, in turn supporting a liquid dispenser, the fraction collectorbeing characterized in that the arm is rotatable about an arm axis andthe liquid dispenser is linearly movable along the arm, the dispenserbeing repositionable above the receptacles as a result of said rotationand as a result of said linear movement along the arm.
 2. A fractioncollector as claimed in claim 1, wherein the arm includes a carriageslideable on a linear bearing to provide said movement of the liquiddispenser along the arm.
 3. A fraction collector as claimed in claim 2 ,wherein the movement of the carriage is caused by a belt connected tothe carriage, in turn driven by a pulley, the pulley being driven by acarriage drive shaft coaxial with the arm axis.
 4. A fraction collectoras claimed in claim 1, wherein the dispenser is disposed, at leastpartially within a slot in the arm and is slideable within the slot. 5.A fraction collector as claimed in claim 1, wherein the axis isperpendicular to the table.
 6. A fraction collector as claimed in claim1, wherein the table includes an upstanding pedestal, the axis runsthrough the pedestal and the rotatably supported on the pedestal.
 7. Afraction collector as claimed in claim 6, wherein the arm is caused torotate about the axis by a driven hollow cylinder mounted for rotationsubstantially within the pedestal.
 8. A fraction collector as claimed inclaim 6, wherein the pedestal is positioned on the table such that twoarrays of receptacles can be accommodated on the table, one on each sideof the pedestal.
 9. A fraction collector as claimed in claim 8, whereinthe arrays of receptacles are mounted to the table in complementaryregister slots, or channels, which match features on the underside ofthe arrays of receptacles.
 10. A fraction collector as claimed in claim1, wherein the table further comprises an extension for mounting of afurther array of receptacles.
 11. A fraction collector as claimed inclaim 3, further including a housing under the table, said housingincluding a carriage motor for driving said carriage drive shaft, and anarm rotation motor for driving the arcuate rotation of the arm via thehollow cylinder.
 12. A fraction collector as claimed in claim 11 whereinthe housing is formed to inhibit the ingress of liquids.
 13. A fractioncollector as claimed in claim 1, wherein wells of the plural receptaclesare arranged in at least one two dimensional array comprising staggeredrows.
 14. A fraction collector comprising a housing protecting driveelements, the top of the housing being formed as a table, the tablehaving at least two receiving positions each for receiving a microplateeach microplate including a plurality of liquid receptacles, and arotatable arm supporting a liquid dispenser, the fraction collectorbeing characterized in that the arm is linearly movable by means of thedrive elements to reposition the dispenser substantially above thereceptacles, said arm having a rotational axis extending generallyperpendicular to the table between the two microplate receivingpositions.
 15. A fraction collector as claimed in claim 14, wherein thereceiving positions include receiving features, for example channels,which allow complementary relative positioning of the table and themicroplates.
 16. Chromatography equipment including the fractioncollector of claim
 1. 17. Chromatography equipment including thefraction collector of claim 14.